Abstract: There are to date no clinical laboratory blood tests for mood disorders. Given the complex nature of mood disorders, the current reliance on patient self-report of symptoms and the clinician's impression on interview of patient is a rate limiting step in delivering the best possible care with existing treatment modalities, as well as in developing new and improved treatment approaches, including new medications. We have provided proof of principle for an approach to help identify blood biomarkers for mood disorders (Le-Niculescu et al. 2009). Such biomarkers can serve as a basis for objective clinical laboratory tests. Our approach to identifying candidate biomarkers is based on the integration of genetic and gene expression studies, in human subjects and animal models. In pilot studies in this area, recently published1 (Le- Niculescu et al. 2009) we have identified a series of high probability blood candidate biomarker genes for mood state that deserve future scrutiny. A predictive score developed based on a panel of ten top candidate biomarkers (five for high mood, five for low mood) shows sensitivity and specificity for high mood (mania) and low mood (depression) states, in two independent patient cohorts. Our preliminary studies suggest that blood biomarkers may offer an unexpectedly informative window into brain functioning and disease state. This high-risk, high reward work needs to be extended and refined, which is what we propose to do. The development of clinical laboratory blood tests for mood disorders such as depression and bipolar disorder will have an impact on patient health, well-being, quality of life, and independent functioning, as well as decrease hospitalizations and overall health-care costs. Given the fact that 1 in 5 people in the US will suffer from a major mood disorder in their lifetime, the potential medical, social and economic impact of such work cannot be overstated. Public Health Relevance: No objective clinical laboratory tests for psychiatric disorders exist to date. The current reliance on imprecise diagnostic classifications, on the patient's self-report of symptoms and the clinicians impression, leads to less than optimal diagnosis and treatment of these prevalent, distressing and disabling conditions. Moreover, the lack of objective diagnostic tests constitutes a significant barrier to the development of new medications and treatment approaches. Our work aims to provide solutions to these problems.